Tox inhibition for the treatment of cancer

Abstract

Described are methods for reducing the proliferation cancer cells by modulating the expression or activity of TOX such as by use of a TOX inhibitor. Inhibiting TOX expression with antisense nucleic acids is shown to reduce the proliferation of malignant T cells. Also described are methods for the treatment of cancer in a subject in need thereof comprising administering to the subject a TOX inhibitor. Optionally, the cancer is a T cell malignancy such as Cutaneous T cell Lymphoma (CTCL).

1 . A method of reducing the proliferation of one or more cancer cells comprising contacting the cancer cells with a TOX inhibitor. 
     
     
         2 .- 16 . (canceled) 
     
     
         17 . A method for treating cancer in a subject in need thereof, comprising modulating the expression or activity of TOX. 
     
     
         18 . The method of  claim 17 , comprising administering to the subject a TOX inhibitor. 
     
     
         19 . The method of  claim 17 , wherein the cancer is T cell malignancy. 
     
     
         20 . The method of  claim 19 , wherein the T cell malignancy is Cutaneous T-cell Lymphoma (CTCL), peripheral T cell lymphoma or T cell leukemia. 
     
     
         21 . The method of  claim 18 , wherein the TOX inhibitor prevents the expression of TOX. 
     
     
         22 . The method of  claim 21 , wherein the TOX inhibitor prevents the transcription of TOX mRNA or translation of TOX protein. 
     
     
         23 . The method of  claim 18 , wherein the TOX inhibitor is a calcineurin inhibitor. 
     
     
         24 . The method of  claim 23 , wherein the calcineurin inhibitor is selected from cyclosporine, FK506 (Tacrolimus), pimerolimus, derivatives thereof and a pharmaceutically acceptable salt thereof. 
     
     
         25 . The method of  claim 23 , wherein the calcineurin inhibitor is FK506 (Tacrolimus). 
     
     
         26 . The method of  claim 18 , wherein the TOX inhibitor is a nucleic acid that binds to a nucleic acid encoding for all or part of TOX. 
     
     
         27 . The method of  claim 26 , wherein the nucleic acid is a small hairpin RNA (shRNA), small interfering RNA (siRNA) or morpholino oligonucleotide. 
     
     
         28 . The method of  claim 18 , wherein the TOX inhibitor binds to the TOX protein, such as a TOX antibody. 
     
     
         29 . The method of  claim 18 , wherein the TOX inhibitor is conjugated to a cell penetrating peptide. 
     
     
         30 . The method of  claim 29 , wherein the cell penetrating peptide is selected from TAT, Angiopep, penetratin, TP, rabies, virus glycoprotein (RVG), prion peptide and SynB. 
     
     
         31 . The method of  claim 18 , wherein the TOX inhibitor is in formulated for transdermal delivery. 
     
     
         32 . The method of  claim 17 , wherein the cancer is Cutaneous T cell malignancy such as Mycosis Fungoides (MF) or Sezary Syndrome. 
     
     
         33 . The method of  claim 17 , further comprising administering to the subject a chemotherapeutic agent. 
     
     
         34 . The method of  claim 33 , wherein the chemotherapeutic agent is selected from methotrexate, retinoids, and a histone deacytylase modifier. 
     
     
         35 . A pharmaceutical composition comprising a TOX inhibitor and a chemotherapeutic agent. 
     
     
         36 .- 39 . (canceled)